2 Fermentation and Biochemical engineering Handbook microorganisms, mammalian cells, plant cells, and tissue. It is our sincere hope that the reader will find this chapter helpful in determining the best conditions for cultivation and the collection of scale-up data. Hopefully, this knowledge will, in turn, facilitate the transformation of worthwhile research programs into commercially viable processes 1.0 MICROBIAL FERMENTATION (by Kuniaki sakato) Chemical engineers are still faced with problems regarding scale- and microbial contamination in the fermentation by aerobic submerged cultures. Despite many advances in biochemical engineering to address these problems, the problems nevertheless persist. Recently, many advances have been made in the area of recombinant DNA, which themselves have spun off new and lucrative fields in the production of plant and animal pharmaceuti cals. A careful study of this technology is therefore necessary, not only for the implementation of efficient fermentation processes, but also for compli ance with official regulatory bodies There are several major topics to consider in scaling up laboratory processes to the industrial level. In general, scale-up is accomplished for a discrete system through laboratory and pilot scale operations. The steps involved can be broken down into seven topics that require some elaboration 1. Strain improvements 2. Optimization of medium composition and cultural condi tions such as pH and temperature 3. Oxygen supply required by cells to achieve the proper metabolic activities 4. Selection of an operative mode for culture process 5. Measurement of rheological properties of cultural broth 6. Modelling and formulation of process control strategies 7. Manufacturing sensors, bioreactors, and other peripheral Items l and 2 should be determined in the laboratory using shake flasks or small jar fermenters. Items 3-7 are usually determined in the pilot plant The importance of the pilot plant is, however, not limited to steps 3-7. The pilot plant also provides the cultured broths needed for downstream2 Fermentation and Biochemical Engineering Handbook microorganisms, mammalian cells, plant cells, and tissue. It is our sincere hope that the reader will find this chapter helpful in determining the best conditions for cultivation and the collection of scale-up data. Hopehlly, this knowledge will, in turn, facilitate the transformation of worthwhle research programs into commercially viable processes. 1.0 MICROBIAL FERMENTATION (by Kuniaki Sakato) Chemical engineers are still faced with problems regarding scale-up and microbial contamination in the fermentation by aerobic submerged cultures. Despite many advances in biochemical engineering to address these problems, the problems nevertheless persist. Recently, many advances have been made in the area of recombinant DNA, which themselves have spun off new and lucrative fields in the production of plant and animal pharmaceuti￾cals. A careful study of this technology is therefore necessary, not only for the implementation of efficient fermentation processes, but also for compli￾ance with official regulatory bodies. There are several major topics to consider in scaling up laboratory processes to the industrial level. In general, scale-up is accomplished for a discrete system through laboratory and pilot scale operations. The steps involved can be broken down into seven topics that require some elaboration: 1. Strain improvements 2. Optimization of medium composition and cultural condi- 3. Oxygen supply required by cells to achieve the proper tions such as pH and temperature metabolic activities 4. Selection of an operative mode for culture process 5. Measurement of rheological properties of cultural broth 6. Modelling and formulation of process control strategies 7. Manufacturing sensors, bioreactors, and other peripheral equipment Items 1 and 2 should be determined in the laboratory using shake flasks or small jar fermenters. Items 3-7 are usually determined in the pilot plant. The importance ofthe pilot plant is, however, not limited to steps 3-7. The pilot plant also provides the cultured broths needed for downstream